Environmental- and Toxin-Induced Lung Diseases

Pathologic Features

Gross Findings

Asbestosis typically ranges in severity from macroscopically normal lungs through minor indurated ill-defined areas in the lower lobes with subpleural accentuation to advanced diffusely contracted lungs with surface pleural bosselation. Cut sections of the lung may reveal fine honeycomb changes ( Fig. 18.1 ). There is often some degree of visceral and, to a lesser extent, parietal pleural thickening and/or plaques. There is only a loose correlation of the extent of these pleural changes with the extent of the lung parenchymal abnormalities.

Microscopic Findings

The CAP-PPS criteria for the microscopic diagnosis of asbestosis require the presence of interstitial fibrosis of an appropriate pattern (always paucicellular and collagenous rather than fibroblastic and inflammatory) and a sufficient number of asbestos bodies. An average rate of at least 2 per cm ² should be present to make a confident diagnosis (based on Perls iron-stained routine thickness sections). Rarely, heavily exposed individuals with appropriate fibrosis have insufficient asbestos bodies in lung tissue to allow for a confident morphologic diagnosis. In such persons, mineral analysis may be performed to show elevated retained asbestos fibers and allows for a diagnosis of asbestosis ex asbestos bodies.

There is a commonly used light microscopic grading system ( Table 18.2 ). The earliest changes are seen around the respiratory bronchioles and first tier of alveoli ( Fig. 18.2 ), but as the disease progresses, the fibrosis extends along alveolar walls and alveolar ducts to link up with other lesions. Eventually, severe disorganization of lung architecture occurs, with honeycomb changes ( Fig. 18.3 ). Other features less commonly encountered are foreign body giant cells around the asbestos bodies, osseous metaplasia, and pulmonary blue bodies, but these are entirely nonspecific.

TABLE 18.2

Light Microscopic Grading Scheme for Asbestosis

Modified from CAP-PPS Roggli schema and 1982 Craighead report.

Grade 1	Fibrosis of the walls of respiratory bronchioles and first adjacent tier of alveoli
Grade 2	Fibrosis around respiratory bronchioles that extends into adjacent alveolar ducts and alveoli but does not join up with fibrosis extending from other respiratory bronchioles
Grade 3	Fibrosis that links up adjacent respiratory bronchioles but with little architectural distortion
Grade 4	Honeycomb changes

An asbestos body is characterized by a clear fibrous core coated by iron-protein-mucopolysaccharide material, which forms a golden-brown, beaded, dumbbell or drumstick-shaped structure ( Figs. 18.4 and 18.5 ). When these cores have been examined by analytical techniques, they are now almost always commercial amphibole fibers. Asbestos bodies rarely, if ever, form on chrysotile fibers. An iron stain can be used to highlight asbestos bodies. However, care has to be taken in identifying asbestos bodies because other material can be coated to form ferruginous bodies, but usually the core has a different appearance and it is not transparent ( Fig. 18.6 ). In persons with marked congestion and hemosiderin deposition in the lungs, the iron stain may be difficult to interpret.

Ancillary Studies

Mineral analysis of bronchoalveolar lavage (BAL) fluid or lung tissue shows high asbestos fiber/body burdens in cases of asbestosis. In a setting of asbestosis, the BAL usually shows a concentration greatly above 1 fiber per mL. It is distinctly unusual for a case of diffuse interstitial fibrosis without asbestos bodies on light microscopy to show lung tissue concentrations of asbestos fibers in the range usually associated with asbestosis.

Phase-contrast light microscopy is technically simple and inexpensive, although it has significant limitations, which include poor optimal resolution and lack of qualitative (fiber typing) information. Transmission electron microscopy (TEM) is the most sensitive method and can detect fibers across the spectrum of sizes. Scanning electron microscopy holds an intermediate position with capacity to provide fiber typing and fiber counting information, although it is less sensitive than TEM.

In a subject with diffuse interstitial fibrosis of appropriate pattern and a retained amphibole asbestos fiber count within the range observed for established asbestosis cases, based on morphologic criteria, the case should be regarded as asbestosis. The asbestosis range refers to the total retained amphibole asbestos fiber content in cases with asbestosis. The chrysotile content is not included because it does not correlate with the grade of fibrosis and reflects the low biopersistence of the fiber. A normal fiber count within the range for nonoccupationally exposed subjects provides strong evidence against a diagnosis of asbestosis.

Differential Diagnosis

In advanced cases, the major differential diagnoses include idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, sarcoidosis, Langerhans cell histiocytosis, and other mineral dust–induced pneumoconioses such as silicosis and siderosis. Asbestosis is usually associated with the presence of numerous asbestos bodies, and this separates it from idiopathic pulmonary fibrosis and the other conditions listed earlier. Also, fibroblast foci are rarely if ever seen in bona fide asbestosis. Temporal and spatial heterogeneity points to the alternative diagnosis of usual interstitial pneumonia, reflecting idiopathic pulmonary fibrosis, a connective tissue disease or hypersensitivity pneumonitis. Granulomas or Langerhans cell aggregates with mixed inflammation would be compatible with sarcoidosis and Langerhans cell histiocytosis, respectively. For diagnosis of the other mineral-induced pneumoconioses such as silicosis and siderosis, characteristic features should be present, such as silicotic nodules in silicosis and pseudoasbestos bodies with yellow or black cores in siderosis.

There are considerable problems in separating grade 1 and 2 lesions of asbestosis from peribronchiolar fibrosis due to cigarette smoking, urban pollution, and other mineral dust–induced lesions. Smoking-related lung fibrosis may be accentuated in subpleural regions and show “ropey” collagen without significant inflammation. These grades of fibrosis are frequent in nonasbestos-exposed individuals, appearing in some 40% of the general population. Such persons often have some degree of emphysema and respiratory bronchiolitis.